This invention is concerned with a chemical process for preparing substituted azetidin-2-ones. In particular it is concerned with a process for the preparation of certain 3.beta.-aminoazetidin-2-ones which are useful intermediates in the synthesis of azetidin-2-one antibiotics for example the antibiotic FR 1923.
The antibiotic FR 1923, also referred to as nocardicin, has been previously described, for example in Belgium Pat. No. 830,934 and by H. Aoki et al., 15th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No. 97, Sept. 1975. Nocardicin has the following structural formula. ##STR1##
Antibiotic FR 1923 has been obtained by culturing Nocardia uniformis var. Tsuyamanensis ATCC 21806 as described by U.S. Pat. No. 3,923,977 issued Dec. 2, 1975.
This invention provides a process for preparing the "nucleus" of nocardicin represented by the following formula, ##STR2## and esters and hydroxy group derivatives thereof.
The nocardicin nucleus is useful in the preparation of nocardicin via acylation with an amino-protected and esterified derivative of 4-(3-amino-3-carboxypropoxy)phenylglyoxylic acid, the acyl side chain of nocardicin. The acylation product, a 3.beta.-phenylglyoxamide azetidin-2-one is deblocked and de-esterified and is converted to nocardicin by formation of the oxime derivative. The synthesis of the acyl side chain of nocardicin and the amino-protected esters thereof is described in co-pending application Ser. No. 739,160 now abandoned filed Nov. 5, 1976 and its continuing application Ser. No. 825,344 filed Aug. 17, 1977.